Identification and Validation of Stromal Immunotype Predict Survival and Benefit from Adjuvant Chemotherapy in Patients with Muscle Invasive Bladder Cancer

Purpose: This study aims to construct the stromal immunotype which could improve prediction of postsurgical survival and adjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC). Patients and Methods: A total of 118 MIBC patients from Shanghai Cancer Center, 140 MIBC patients from Zhongshan hospital and 287 MIBC patients from TCGA cohort were included in the study. Immune cell infiltration was evaluated by immunohistochemical staining or CIBERSORT method. Five immune features were selected out of 22 immune features to construct immunotype based on LASSO Cox regression model. Result: Using the LASSO model, we classified MIBC patients into stromal immunotype A subgroup (CTL high NK high Treg low Macrophage low MC low) and stromal immunotype B subgroup (CTL low NK low Treg high Macrophage high MC high). Significant differences were found between immunotype A and immunotype B in the combined cohort with 5-year overall survival (76.0% vs. 44.0%; P<0.001) and 5-year disease-free survival (62.8% vs. 48.3%; P<0.001). Stromal immunotype was revealed to be an independent prognostic indicator in multivariate analysis in all cohorts separately. Either overall survival or disease-free survival was not improved by adjuvant chemotherapy (ACT) in pT2 stage patients or pT3+pT4 patients. But further analysis revealed that overall survival and disease-free was significantly improved by ACT in pT3+pT4 patients. (P=0.016 and P=0.006, respectively). Finally, stromal immunotype A showed higher immune checkpoint molecules (PD-L1, PD-1, CTLA-4) expression. Conclusion: The stromal immunotypes could predict survival and recurrence of MIBC effectively. Furthermore, the immunotypes might be a practical predictive tool to identify pT3+pT4 patients who would benefit from ACT.

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